Time-resolved Laue crystallography, as its name implies, can only be performed on crystalline samples. The intermolecular forces that maintain crystalline order constrain large amplitude conformational motion, and this loss of flexibility may perturb or even inhibit the function of a protein. Nonetheless, Laue crystallography stands alone in its ability to track structural changes in proteins on ultrafast time scales with near atomic spatial resolution. X-rays can also extract structural information from molecules in solution where the full range of conformational motion is permitted. However, without external alignment forces, the protein molecules are randomly oriented, and the structural information contained in its orientationally-averaged, diffuse scattering pattern is one dimensional. It is well known that the Small-Angle X-ray Scattering (SAXS) region of the scattering pattern reports on the size and shape of the protein, while the Wide-Angle X-ray Scattering (WAXS) region is sensitive to secondary and tertiary structure. Together, the SAXS/WAXS scattering patterns provide fingerprints that can be correlated with protein structure via molecular models. Time-dependent changes of the SAXS/WAXS fingerprint can therefore be used to assess which models best describe the reaction pathway in solution. Thus, progress in this area requires close connections between experiment and theory. Our time-resolved SAXS/WAXS methodology is based on the pump-probe method, in which a laser pulse triggers a structural change in the protein, and a delayed x-ray pulse probes the proteins structure through its scattering pattern. We initially pursued time-resolved WAXS studies at the ESRF, but our studies there suffered from a lack of sufficient beamtime. Thus, we invested much effort to develop the infrastructure required to pursue time-resolved X-ray scattering studies on the BioCARS beamline at the APS, and expanded our goals to access the SAXS region as well. We reported in 2010 the ability to acquire, for the first time, time-resolved SAXS/WAXS patterns with 100 ps time resolution. Numerous innovations made this demonstration experiment possible. For example, our diffractometer design allows us to acquire both SAXS and WAXS data on the same detector at the same time over a range of q (momentum transfer) spanning 0.02 to 2.6 inverse Angstroms This large dynamic range of q includes the water ring, which can be used to scale images before calculating their differences. Accurate scaling is crucial when computing time-resolved scattering differences and when subtracting buffer scatter from protein scatter in static SAXS/WAXS measurements. Instead of flowing the protein solution through a capillary during x-ray exposure, we employ a rapid translation stage capable of more than 1g acceleration, and translate the sample capillary after each pump-probe pair in a move-stop-acquire data collection protocol. The translation stage moves at a repetition frequency up to 41 Hz, a frequency that allows acquisition of time-resolved scattering patterns spanning time delays from 100 ps to 10 ms. Data acquired at longer time delays requires reducing the repetition rate below 41 Hz. After integrating the x-rays from many pump-probe pairs (up to 1100), the detector is read, and a syringe pump introduces fresh protein solution into the interaction region of the capillary. We have used this infrastructure to investigate the photocycle of photoactive yellow protein (PYP) in solution, which has long served as a model system for investigating signaling in proteins. Our time-resolved Laue crystallography studies of this protein are described in a separate report. Briefly, we characterized structural transitions in PYP spanning 10 decades of time, from 100 ps to 1 s, and identified 4 intermediates, the last of which presumably produces the signaling state. Photoactivation of PYP triggers trans-to-cis isomerization of p-coumaric acid (pCA), which shortens the distance between its sulfur and phenolate oxygen by 0.7 Angstroms, and like a winch, shortens the distance between the helices to which it and its hydrogen bonding partners are attached. Because the pCA chromophore absorbs light polarized along it long axis, proteins whose chromophore is nominally aligned with the laser excitation polarization will be photoselected, which should produce an anisotropic distribution of photoactivated protein molecules, and should produce an anisotropic SAXS scattering pattern. We have exploited this principle of photoselection and the method of time-resolved SAXS to investigate protein size and shape changes following photoactivation of PYP in solution with 150 ps time resolution. This study partially overcomes the orientational average intrinsic to solution scattering methods, and provides structural information at a higher level of detail. Photoactivation of the pCA chromophore in PYP produces a highly-contorted, short-lived, red shifted intermediate (pR0), and triggers prompt, protein compaction of approximately 0.3% along the direction defined by the electronic transition dipole moment of the chromophore. Contraction along this dimension is accompanied by expansion along the orthogonal directions, with the net protein volume change being approximately -0.25%. More than half the strain arising from formation of pR0 is relieved by the pR0 to pR1 structure transition (1.8 +/- 0.2 ns), with the persistent strain presumably contributing to the driving force needed to generate the spectroscopically blue-shifted pB signaling state. These results are consistent with the near-atomic resolution structural dynamics reported in a recent time-resolved Laue crystallography study of PYP crystals, and suggest that the early-time structural dynamics in the crystalline state carry over to proteins in solution. This past year, we developed a new, slotted sample cell that is supported on a high-precision TEC-based temperature controller capable of operating from 0 to 120 C. We also developed a high-speed diffractometer capable of 1g acceleration on all three axes (XYZ) with 1-2 um positioning accuracy. Our new generation SAXS/WAXS sample cell is mounted on this diffractometer, which makes it easy to align, and facilitates operation at different laser penetration depths. As this methodology becomes easier to use, we expect it to become an ever more important complement to time-resolved Laue studies and time-resolved optical spectroscopy studies of proteins, and will help provide a structural basis for understanding how proteins function.